D3.158 - Dupilumab Response in a Patient with Severe Asthma Refractory to Anti-IL5 Therapy: A Case Report

A 42-year-old woman had been followed with a diagnosis of asthma for six years. During the last year, she experienced a significant worsening of symptoms, including daily dyspnea and frequent coughing attacks. In this period, she had been hospitalized ten times, received at least five courses of outpatient oral corticosteroids (OCS), and had multiple emergency department visits.

She had no history of smoking, obesity, gastroesophageal reflux disease, obstructive sleep apnea symptoms, or other chronic comorbidities. She had a cat at home and reported only rare rhinitis symptoms. Her family history was notable for asthma in her father.

Her maintenance therapy included regular inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), montelukast, and frequent use of nebulized short-acting beta-agonist and short-acting muscarinic antagonist due to daily symptoms. On physical examination, she had diffuse bilateral wheezing with prolonged expiration. Her Asthma Control Test (ACT) score at presentation was 5.

Laboratory evaluation showed peripheral blood eosinophil counts ranging from 360 to 490 cells/µL over the last two years, mostly measured while on systemic corticosteroids. Total serum IgE was 236 IU/mL. Thoracic computed tomography was normal, whereas paranasal sinus CT revealed pansinusitis without nasal polyps.

Treatment and Follow-Up

After optimization of inhaled therapy with the addition of tiotropium, asthma control remained poor. Therefore, benralizumab was initiated; however, no significant clinical improvement was observed. The treatment was switched to mepolizumab, but the patient continued to experience frequent exacerbations and emergency department visits.

Fractional exhaled nitric oxide (FeNO) was subsequently measured and found to be 32 ppb. Due to persistent uncontrolled asthma, dupilumab therapy was initiated.

Following dupilumab treatment, the patient experienced complete resolution of asthma exacerbations and had no further emergency visits. Her ACT score improved to 20, and spirometric parameters showed marked improvement.(The image shows spirometry results before and after dupilumab administration). She has remained exacerbation-free during follow-up.

Discussion and Conclusion

This case highlights a patient with severe asthma exhibiting eosinophilic and allergic features who failed to respond to anti-IL5 therapies but demonstrated a dramatic response to IL-4/13 pathway blockade with dupilumab. The case underscores the heterogeneity of severe asthma and emphasizes that biologic selection should not rely solely on blood eosinophil levels but should also consider coexisting allergic components and other Type-2 biomarkers such as FeNO.

In patients with severe eosinophilic and allergic asthma who are unresponsive to anti-IL5 therapy, dupilumab may represent a highly effective alternative. This report illustrates the importance of biologic switching strategies in the personalized management of severe asthma.